本文選題：氨基酸 + 高效液相色譜串聯(lián)質(zhì)譜法　； 參考：《第二軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：【背景及目的】急性腎損傷(Acute Kidney Injury,AKI)是腎臟結(jié)構(gòu)和功能受損的一種疾病狀態(tài),以突發(fā)和持續(xù)的腎功能下降為特征,是由不同病因?qū)е碌�、涉及全身各系統(tǒng)癥狀的臨床綜合征。2013年我國約有290萬住院患者罹患AKI,死亡率約24%。AKI的發(fā)生增加了住院患者醫(yī)療費用和死亡率,同時造成醫(yī)療資源的浪費。目前AKI的診斷主要依靠血肌酐的升高和尿量的減少,而這兩個指標(biāo)對AKI的診斷較為滯后,不能及時反映患者腎臟的真實損傷情況,發(fā)掘新的有效AKI早期診斷標(biāo)志物有助于解決當(dāng)前AKI的診斷不足。腎臟參與體內(nèi)多種氨基酸的代謝與排泄過程,體內(nèi)氨基酸水平受到腎臟功能的調(diào)節(jié),腎臟功能受到損傷時常發(fā)生氨基酸代謝紊亂。近年來研究發(fā)現(xiàn),多種氨基酸水平與腎臟疾病患者的腎功能和預(yù)后顯著相關(guān),如非對稱二甲基精氨酸、對稱二甲基精氨酸、S-腺苷同型半胱氨酸等。由此可見氨基酸可能成為發(fā)掘有效AKI早期診斷標(biāo)志物新的研究群體。本研究應(yīng)用課題組前期建立的靶向氨基酸定量分析技術(shù),以腎臟缺血再灌注大鼠和心臟手術(shù)患者為研究對象,進(jìn)行氨基酸分析和AKI標(biāo)志物篩選。AKI是急性腎病的一種狀態(tài)同時與慢性腎病關(guān)系密切,一方面AKI可以在慢性腎病的基礎(chǔ)上發(fā)生,另一方面部分AKI患者腎功能未能完全恢復(fù)也可能進(jìn)展為慢性腎損傷。因此,我們還對慢性腎病患者體內(nèi)氨基酸代謝紊亂情況進(jìn)行了研究,探索氨基酸標(biāo)志物對慢性腎病的診斷作用,以拓展氨基酸標(biāo)志物的應(yīng)用范圍。【材料與方法】1、建立大鼠腎臟缺血再灌注模型,采集AKI發(fā)生后24小時內(nèi)的多時間點血清樣本進(jìn)行23種氨基酸定量分析并篩選氨基酸標(biāo)志物,采用受試者工作曲線評估氨基酸標(biāo)志物對AKI的診斷情況,并與肌酐、尿素氮以及中性粒細(xì)胞明膠酶相關(guān)載脂蛋白進(jìn)行比較。2、以心臟手術(shù)患者為研究對象,采集患者術(shù)后24小時內(nèi)的多時間點血漿樣本進(jìn)行23種氨基酸定量分析。篩選氨基酸標(biāo)志物,并對標(biāo)志物進(jìn)行AKI診斷分析。3、收集慢性腎病患者和健康志愿者血漿樣本,篩選兩組患者間差異氨基酸,分析差異氨基酸對慢性腎病的診斷作用�！狙芯拷Y(jié)果】1、腎臟缺血再灌注大鼠血漿對稱二甲基精氨酸、犬尿氨酸、馬尿酸和氧脯氨酸水平在損傷后24小時內(nèi)均對AKI具有診斷作用。四種氨基酸標(biāo)志物從腎臟損傷后1小時開始對AKI具有較好的診斷作用,其中犬尿氨酸和馬尿酸對AKI的診斷作用最佳,診斷能力高于中性粒細(xì)胞明膠酶相關(guān)載脂蛋白和血肌酐水平。2、心臟手術(shù)患者血漿對稱二甲基精氨酸和馬尿酸水平在術(shù)后多個時間具有AKI診斷作用。對稱二甲基精氨酸從12小時開始對AKI具有診斷作用,且診斷能力高于術(shù)后12小時血肌酐;馬尿酸水平在術(shù)后8小時開始對AKI具有診斷作用,診斷效能與12小時血肌酐水平相當(dāng),但診斷時間更早。3、對稱二甲基精氨酸作為腎功能標(biāo)志物不僅可以用于AKI的診斷,對慢性腎病也具有較高的診斷能力。此外,慢性腎病患者體內(nèi)氨基酸代謝紊亂還包括色氨酸、酪氨酸、賴氨酸、纈氨酸、對稱二甲基精氨酸、甲硫氨酸、組氨酸和亮氨酸;這些氨基酸水平均對慢性腎病具有較好的診斷效果�！窘Y(jié)論】研究結(jié)果表明,課題組建立的靶向氨基酸技術(shù)可應(yīng)用于腎前性因素導(dǎo)致的AKI,并由此發(fā)現(xiàn)具有早期診斷功能的代謝標(biāo)志物,其中對稱二甲基精氨酸和馬尿酸水平在大鼠AKI模型中以及心臟手術(shù)患者中均具有較好的早期診斷效果。此外,臨床研究結(jié)果表明對稱二甲基精氨酸還能應(yīng)用于慢性腎病的診斷。
[Abstract]:[background and purpose] Acute Kidney Injury (AKI) is a disease state of impaired renal structure and function. It is characterized by sudden and persistent decline in renal function. It is caused by different causes. In the year of the clinical syndrome involving systemic symptoms, about 2 million 900 thousand of our hospitalized patients suffered from AKI and the mortality rate was about 24%.AKI in.2013. At present, the diagnosis of AKI mainly depends on the increase of serum creatinine and the decrease of urine volume, and the diagnosis of the two indexes is lagging behind the diagnosis of AKI, which can not reflect the real damage of the kidney in time, and discover new effective AKI early diagnostic markers. It helps to solve the deficiency of the current AKI diagnosis. The kidney participates in the metabolism and excretion of various amino acids in the body. The level of amino acids in the body is regulated by the renal function and the renal function is damaged by the impairment of amino acid metabolism. In recent years, many amino acid levels have been found to be significantly related to renal function and prognosis in patients with renal disease. Such as asymmetric two methyl arginine, symmetric two methyl arginine, S- adenosine homocysteine, and so on. This shows that amino acids may be a new research group to explore the early diagnostic markers of effective AKI. This study used the target amino acid quantitative analysis technique established by the group in the early stage for renal ischemia reperfusion rats and patients with cardiac surgery. For the study, amino acid analysis and AKI marker screening.AKI are one of the states of acute kidney disease and chronic kidney disease. On the one hand, AKI can occur on the basis of chronic kidney disease. On the other hand, some AKI patients have not fully recovered the renal function and may progress to chronic renal injury. Therefore, we also have chronic kidney disease. The disorder of amino acid metabolism in the patient was studied in order to explore the diagnostic effect of amino acid markers on chronic kidney disease in order to expand the application of amino acid markers. [materials and methods] 1, a rat model of renal ischemia reperfusion was established, and 23 kinds of amino acid quantitation were collected from the multiple time point serum samples within 24 hours after the occurrence of AKI. Analysis and screening of amino acid markers, using the subjects' work curve to evaluate the diagnosis of amino acid markers on AKI, and compare.2 with creatinine, urea nitrogen and neutrophil gelatinase related apolipoprotein. In heart surgery patients, 23 kinds of ammonia were collected at 24 hours after the operation. Quantitative analysis of basic acid, screening of amino acid markers, and AKI diagnosis and analysis of the markers.3, collection of chronic renal disease and healthy volunteers plasma samples, screening two groups of patients with differential amino acids, analysis of differential amino acids for chronic renal disease diagnosis. [results] 1, renal ischemia reperfusion rat plasma symmetric two methyl semen The levels of ammonia, canine urinary ammonia, uric acid and proline were all diagnostic to AKI within 24 hours after injury. The four amino acid markers had a better diagnostic effect on AKI from 1 hours after renal injury. The diagnostic ability of canine urinary ammonia and uric acid for AKI was better than that of neutrophil gelatinase related load. The level of lipoprotein and serum creatinine was.2, and the plasma symmetric two methylarginine and the level of dianine had a AKI diagnostic effect at many times after the operation. Symmetric two methyl arginine had a diagnostic effect on AKI from 12 hours, and the diagnostic ability was higher than 12 hours after the operation; the level of urine acid began to AKI at 8 hours after the operation. The diagnostic efficacy is equal to 12 hours serum creatinine level, but the diagnosis time is earlier.3. Symmetric two methyl arginine as a renal function marker can not only be used in the diagnosis of AKI, but also have high diagnostic ability for chronic kidney disease. Valine, symmetrical two methyl arginine, methionine, histidine, and leucine, these amino acid levels have a good diagnostic effect on chronic kidney disease. [Conclusion] the results of the study suggest that the target amino acid technique established by the group can be applied to AKI induced by pre renal factors, and thus the metabolic markers that have early diagnostic functions are found. In the AKI model of rats and the patients with cardiac surgery, symmetrical two methyl arginine and dianine have good early diagnosis effect. In addition, the clinical results show that symmetric two methylarginine can be used in the diagnosis of chronic kidney disease.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692

【參考文獻(xiàn)】

中國期刊全文數(shù)據(jù)庫 前1條

1 董春霞;楊莉;;AKI的流行病學(xué):AKI的發(fā)生率、患者死亡率、腎臟死亡率[J];中國血液凈化;2017年01期

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本文編號：1974949